France - Services in the field of biology and pathophysiology of neuromuscular diseases

Description

LMNA-related dilated cardiomyopathy (LMNA-DCM) is a serious, inherited disease caused by mutations in the LMNA gene. This gene provides instructions for the manufacture of proteins called A-type lamins (A/C lamins), which help maintain the structure of the cell nucleus and play an important role in regulating chromatin organization, gene expression and cytoskeletal organization by interacting with numerous other proteins. Currently, there is no effective treatment for LMNA-DCM as we do not fully understand the underlying mechanisms of the disease. Objective 2 investigates the underlying disease mechanism(s) contributing to LMNA-DCM, by uncovering the complex cellular and molecular processes underlying disease pathogenesis and progression using state-of-the-art technologies.
The services to be provided are as follows:
- Quantitative assessment of the global architecture of the MT network, the distribution of tubulin post-translational modifications and MT dynamics in LMNA mutant and healthy control iPSC-CMs, as well as in adult mouse cardiomyocytes.
- Testing whether targeting post-translational modifications of disrupted MTs improves cytoskeletal and nuclear structure and function. Elucidation of how the MT cytoskeleton is modified in LMNA-DCM and how these modifications contribute to disease pathogenesis could provide new means of preserving cardiac structure and function in LMNA-DCM, as well as in other cardiomyopathies in which MT organization is disrupted.
- Quarterly reporting.

Opportunity closing date

27 January 2025

Value of contract

to be confirmed